Single prolonged stress: toward an animal model of posttraumatic stress disorder

Although selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in decreasing posttraumatic stress disorder (PTSD) symptoms, a subgroup of PTSD patients remain chronically symptomatic and maintain conditioned fear responses to traumatic stimuli. In this context, the establishment of an appropriate animal model of PTSD is necessary to promote better understanding of the mechanisms of the disorder and to facilitate the development of more effective therapeutic alternatives to SSRIs. Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD. SPS rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior and glucocorticoid negative feedback, and they exhibit the expected therapeutic response to paroxetine on enhanced fear memory. In addition, SPS rats exhibit enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which is alleviated by D -cycloserine. The enhanced consolidation and impaired extinction of fear memory found in SPS rats suggests that this model has additional value because recent studies of PTSD indicate that memory abnormalities are a central feature. In this study, we summarize the behavioral and pathophysiological PTSD-like symptoms in SPS, focusing on memory abnormalities, and evaluate the validity of SPS as an animal model of PTSD. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64546/1/20629_ftp.pd

Left Behind: Despite Positive Attitudes, Learning Is Modulated by Prior Academic Achievement

In our Introductory Psychology (Psych 100) program, 30 graduate TAs/faculty teach 2,700 undergraduates annually. While the program has received many accolades and TAs are often recognized for their teaching skills, we have not systematically investigated the program’s strengths and weaknesses. Accordingly, in Fall 2009, we studied 3 questions: 1. What are students’ attitudes toward the course? 2. Do students in Psych 100 learn the core psychological concepts? 3. Are there differences in learning based on students’ characteristics

Because You Can\u27t Teach It All and They Won\u27t Read It All: Student Response Systems Do Improve Learning

In Introductory Psychology, 30 graduate TAs/faculty teach 2700 students annually. This year we developed an assessment program to improve student learning and graduate teaching training (Shigeto et al., 2010). Part of the program studied the pedagogical value of using student response systems to answer in-class multiple choice questions. Prior research lacks scientific rigor and provides equivocal evidence that SRSs improve learning (Caldwell, 2007)

Typologies of stress appraisal and problem-focused coping: associations with compliance with public health recommendations during the COVID-19 pandemic.

BACKGROUND: Given prior research finding that young adults are less likely to engage in recommended public health behaviors (PHBs) than older adults, understanding who is and is not likely to engage in PHBs among young adults is crucial to mitigating the effects of the COVID-19 pandemic. Drawing on the Transactional Theory of Stress and Coping, this study examined how typologies of stress appraisal (SA) and problem-focused coping (PFC) among young adults were associated with compliance with public health recommendations during the pandemic. METHODS: An online sample of young adults in the United States, ages 18-35, was recruited during the early phase of the pandemic (April-May 2020). Participants reported their appraisals of how central, threatening, and uncontrollable the pandemic was, their tendencies to engage in instrumental, problem-focused coping strategies, and how frequently they engaged in three recommended PHBs (social distancing, mask wearing, and hand washing). RESULTS: Using latent class analysis, we identified three classes of individuals: Low-SA/Low-PFC, Low-SA/High-PFC, and High-SA/High-PFC. Demographics did not efficiently distinguish membership in the three classes. The former two classes reported less compliance with public health recommendations than did the latter class. Tests of measurement invariance for gender indicated trivial differences in the composition of class membership and relations to compliance. CONCLUSIONS: This research uncovered three qualitatively distinct classes of people who differed in their appraisal of the pandemic and their tendency to engage in PFC. Individuals who view the pandemic as central and threatening and engage in problem-focused coping were more likely than their peers to comply with guidelines recommending social distancing, mask wearing, and hand washing. These results contribute to our understanding of why people do and do not comply with public health guidelines and highlight the importance of attending to psychological variables in public health research. Understanding what drives poor compliance with public health recommendations can contribute to efforts promoting better compliance, and ultimately better health outcomes

Parents’ differential susceptibility to the effects of marital quality on sensitivity across the first year

The current investigation examined the differential susceptibility of parents to the effects of marital quality on changes in parenting. We predicted that parents who were high on the personality constructs Negative Affect and Constraint would be more susceptible to the effects of marital quality on their level of sensitivity. Sensitivity was assessed at 3.5 and 13 months for both mothers and fathers during a triadic interaction. Consistent with the differential susceptibility theory, results suggested that when mothers were high on Negative Affect and when fathers were high on Constraint, their marital quality was associated with changes in sensitivity. This investigation suggests that personality factors may create “vulnerabilities” in parents that make them differentially susceptible to the effects of the family environment on parentin

Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study

INTRODUCTION: TNFAIP3 interacting protein 1, TNIP1 (ABIN-1) is involved in inhibition of nuclear factor-κB (NF-κB) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent genome-wide association studies revealed association of TNIP1 with SLE in the Caucasian and Chinese populations. In this study, we investigated whether the association of TNIP1 with SLE was replicated in a Japanese population. In addition, association of TNIP1 with RA was also examined. METHODS: A case-control association study was conducted on the TNIP1 single nucleotide polymorphism (SNP) rs7708392 in 364 Japanese SLE patients, 553 RA patients and 513 healthy controls. RESULTS: Association of TNIP1 rs7708392C was replicated in Japanese SLE (allele frequency in SLE: 76.5%, control: 69.9%, P = 0.0022, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.13-1.74). Notably, the risk allele frequency in the healthy controls was considerably greater in Japanese (69.9%) than in Caucasians (24.3%). A tendency of stronger association was observed in the SLE patients with renal disorder (P = 0.00065, OR 1.60 [95%CI 1.22-2.10]) than in all SLE patients (P = 0.0022, OR 1.40 [95%CI 1.13-1.74]). Significant association with RA was not observed, regardless of the carriage of human leukocyte antigen DR β1 (HLA-DRB1) shared epitope. Significant gene-gene interaction between TNIP1 and TNFAIP3 was detected neither in SLE nor RA. CONCLUSIONS: Association of TNIP1 with SLE was confirmed in a Japanese population. TNIP1 is a shared SLE susceptibility gene in the Caucasian and Asian populations, but the genetic contribution appeared to be greater in the Japanese and Chinese populations because of the higher risk allele frequency. Taken together with the association of TNFAIP3, these observations underscore the crucial role of NF-κB regulation in the pathogenesis of SLE

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype

ObjectiveAutoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.MethodsHLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.ResultsThe predisposing association of DRB1*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62–5.43), DRB1*04:05 (P = 1.89×10−21, Pc = 5.86×10−20, OR 3.41, 95% CI 2.65–4.38), and DQB1*04:01 (P = 4.66×10−18, Pc = 6.99×10−17, OR 3.89, 95% CI 2.84–5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32–0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10−9, OR 3.52, 95% CI 2.34–5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45–424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10−6, OR 10.64, 95% CI 3.19–35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.ConclusionsThe important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes

TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study

IntroductionThe Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. A recent multicenter study in East Asian populations, comprising Chinese, Korean and Japanese participants, identified an association of a TLR7 single-nucleotide polymorphism (SNP) located in the 3\u27 untranslated region (3\u27 UTR), rs3853839, with systemic lupus erythematosus (SLE), especially in males, although some difference was observed among the tested populations. To test whether additional polymorphisms contribute to SLE in Japanese, we systematically analyzed the association of TLR7 with SLE in a Japanese female population.MethodsA case-control association study was conducted on eight tag SNPs in the TLR7 region, including rs3853839, in 344 Japanese females with SLE and 274 healthy female controls.ResultsIn addition to rs3853839, two SNPs in intron 2, rs179019 and rs179010, which were in moderate linkage disequilibrium with each other (r2 = 0.53), showed an association with SLE (rs179019: P = 0.016, odds ratio (OR) 2.02, 95% confidence interval (95% CI) 1.15 to 3.54; rs179010: P = 0.018, OR 1.75, 95% CI 1.10 to 2.80 (both under the recessive model)). Conditional logistic regression analysis revealed that the association of the intronic SNPs and the 3\u27 UTR SNP remained significant after we adjusted them for each other. When only the patients and controls carrying the risk genotypes at the 3\u27 UTR SNPpositionwere analyzed, the risk of SLE was significantly increased when the individuals also carried the risk genotypes at both of the intronic SNPs (P = 0.0043, OR 2.45, 95% CI 1.31 to 4.60). Furthermore, the haplotype containing the intronic risk alleles in addition to the 3\u27 UTR risk allele was associated with SLE under the recessive model (P = 0.016, OR 2.37, 95% CI 1.17 to 4.80), but other haplotypes were not associated with SLE.ConclusionsThe TLR7 intronic SNPs rs179019 and rs179010 are associated with SLE independently of the 3\u27 UTR SNP rs3853839 in Japanese women. Our findings support a role of TLR7 in predisposition for SLE in Asian populations

Protective Role of HLA-DRB1*13:02 against Microscopic Polyangiitis and MPO-ANCA-Positive Vasculitides in a Japanese Population: A Case-Control Study

Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1*09:01-DQB1*03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3x10-4 by applying Bonferroni correction. The association of DRB1*09:01 with MPO-AAV was confirmed (allele model, P = 2.1x10-4, odds ratio [OR] = 1.57). Protective association of DRB1*13:02 was detected against MPO-AAV (allele model, P = 2.3x10-5, OR = 0.42) and MPA (dominant model, P = 2.7x10-4, OR = 0.43). A trend toward increased frequency of DPB1*04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1*13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1*04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1*13:02 (Padjusted = 0.16), suggesting that DRB1*13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1*04:01 with PR3-AAV and MPO-AAV and difference in DPB1*04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1*13:02 was suggested to be a shared protective factor against multiple autoimmune diseases